Identification and characterization of novel mammalian neuropeptide FF-like peptides that attenuate morphine-induced antinociception.

The two mammalian neuropeptides NPFF and NPAF have been shown to have important roles in nociception, anxiety, learning and memory, and cardiovascular reflex. Two receptors (FF1 and FF2) have been molecularly identified for NPFF and NPAF. We have now characterized a novel gene designated NPVF that encodes two neuropeptides highly similar to NPFF. NPVF mRNA was detected specifically in a region between the dorsomedial and ventromedial hypothalamic nuclei. NPVF-derived peptides displayed higher affinity for FF1 than NPFF-derived peptides, but showed poor agonist activity for FF2. Following intracerebral ventricular administration, a NPVF-derived peptide blocked morphine-induced analgesia more potently than NPFF in both acute and inflammatory models of pain.

In situ hybridization analysis revealed distinct expression patterns of FF1 and FF2 in the rat central nervous system. FF1 was broadly distributed, with the highest levels found in specific regions of the limbic system and the brainstem where NPVF-producing neurons were shown to project. FF2, in contrast, was mostly expressed in the spinal cord and some regions of the thalamus.

These results indicate that the endogenous ligands for FF1 and FF2 are NPVF- and NPFF-derived peptides, respectively, and suggest that the NPVF/FF1 system may be an important part of endogenous anti-opioid mechanism.
Liu Q, et al. J Biol Chem 2001 Oct 5;276(40):36961-9

A New human gene that encodes at least three neuropeptides containing carboxy-terminal RFamide, hRFRP1, hRFRP2 and hRFRP3, has been identified.  CHO cells  transfected with a rat orphan G protein-coupled receptor, OT7T022, specifically respond to synthetic hRFRP1 and hRFRP3. RFRP and OT7T022 receptor mRNA are expressed in particular regions of the rat hypothalamus, and intracerebroventricular administration of hRFRP-1 increases prolactin secretion  in a manner that is different from that of Prolactin-releasing peptide, another RFamide peptide.

These results indicated that a variety of RFamide-related peptides may exist and function in mammals.
Hinuma S., et al. Nature cell Biology, 2, 703~708 (October 2000)